Craniofacial malformations are among the most common birth defects in children and lead to substantial morbidity and mortality for these infants. Despite the severity of the illness, little is known about the molecular mechanisms that are necessary for correct formation of facial structures. In this proposal, we will investigate craniofacial development in an emerging model system, Xenopus tropicalis. During a recent forward genetic screen, we identified two mutants, jaws and jawbreaker, that exhibit a specific embryonic defect in the development of craniofacial structures. These mutants show a simple Mendelian inheritance pattern suggestive of a single recessive mutant locus. Outside of the craniofacial defect, the remainder of the embryo appears wildtype. It is the goal of this proposal to characterize these two mutants and identify where and when during development craniofacial patterning begins to fail. In a second aim, we will attempt to identify the mutant locus which will greatly improve our understanding of the molecular patterning defect. Because our understanding of craniofacial morphogenesis remains superficial, characterizing these mutants has the potential of substantially improving our understanding of craniofacial development and malformations. In addition, this will represent one of the very first attempts to clone a mutant identified in a forward genetic screen in X. tropicalis. Successful completion of these goals will greatly support future genetic screens in this emerging model system. Birth defects of the head and neck are a common cause of serious illness in infants. Yet, our scientific understanding of how these structures form during embryonic development remains superficial. We propose a series of experiments to analyze two frog mutants that have abnormal jaw structure. A better understanding of these frog mutants can then be used as a model to understand birth defects of the head and neck in humans.